Exploring miRNA-mRNA regulatory network in cardiac pathology in Na+ /H+ exchanger isoform 1 transgenic mice

Physiological Genomics
Jin XueGabriel G Haddad

Abstract

Numerous studies have demonstrated that Na+/H+ exchanger isoform 1 (NHE1) is elevated in myocardial diseases and its effect is detrimental. To better understand the involvement of NHE1, we have previously studied cardiac-specific NHE1 transgenic mice and shown that these mice develop cardiac hypertrophy, interstitial fibrosis, and cardiac dysfunction. The purpose of current study was to identify microRNAs and their mRNA targets involved in NHE1-mediated cardiac injury. An unbiased high-throughput sequencing study was performed on both microRNAs and mRNAs. RNA sequencing showed that differentially expressed genes were enriched in hypertrophic cardiomyopathy pathway by Kyoto Encyclopedia of Genes and Genomes annotation in NHE1 transgenic hearts. These genes were classified as contraction defects (e.g., Myl2, Myh6, Mybpc3, and Actb), impaired intracellular Ca2+ homeostasis (e.g., SERCA2a, Ryr2, Rcan1, and CaMKII delta), and signaling molecules for hypertrophic cardiomyopathy (e.g., Itga/b, IGF-1, Tgfb2/3, and Prkaa1/2). microRNA sequencing revealed that 15 microRNAs were differentially expressed (2-fold, P < 0.05). Six of them (miR-1, miR-208a-3p, miR-199a-5p, miR-21-5p, miR-146a-5p, and miR-30c-5p) were reported to be related to ...Continue Reading

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Datasets Mentioned

BETA
SRP118869

Methods Mentioned

BETA
transgenic
RNA-Seq
PCR
Illumina Sequencing
miRNA-Seq
nuclear translocation

Software Mentioned

NIH Image
URA
Ingenuity Pathway Analysis ( IPA )
Ingenuity Pathway Analysis
Upstream Regulator Analysis ( URA )
TargetScan
miRanalyzer
Cufflinks
ImageJ
Ingenuity Pathways Analysis ( IPA )

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